[Risk modeling based on HER-2 related genes for bladder cancer survival prognosis assessment].

OBJECTIVE: To investigate the correlation between the human epidermal growth factor receptor-2-related genes (HRGs) and survival prognosis of bladder cancer and to construct a predictive model for survival prognosis of bladder cancer patients based on HRGs. METHODS: HRGs in bladder cancer were found by downloading bladder tumor tissue mRNA sequencing data and clinical data from the cancer genome atlas (TCGA), downloading HER-2 related genes from the molecular signatures database (MsigDB), and crossing the two databases. Further identifying HRGs associated with bladder cancer survival (P < 0.05) by using single and multi-factor Cox regression analysis and constructing HRGs risk score model (HRSM), the bladder cancer patients were categorized into high-risk and low-risk groups accor-ding to the median risk score. Survival analysis of the patients in high- and low-risk groups was conducted using R language and correlation of HRGs with clinical characteristics. A multi-factor Cox regression analysis was used to verify the independent factors affecting the prognosis of the patients with bladder cancer. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of HRSM was calculated, and a nomogram was constructed for survival prediction of the bladder cancer patients. Analysis of HRSM and patient immune cell infiltration correlation was made using the TIMER database. RESULTS: A total of 13 HRGs associated with patient survival were identified in this study. Five genes (BTC, CDC37, EGF, PTPRR and EREG) were selected for HRSM by multi-factor Cox regression analysis. The 5-year survival rate of the bladder cancer patients in the high-risk group was significantly lower than that of the patients in the low-risk group. High expression of PTPRR was found to be significantly and negatively correlated with tumor grade and stage by clinical correlation analysis, while EREG was found to be the opposite; Increased expression of EGF was associated with high grade, however, the high expression ofCDC37showed the opposite result. And no significant correlation was found between BTC expression and clinical features. Correlation analysis of HRSM with immune cells revealed a positive correlation between risk score and infiltration of dendritic cells, CD8+T cells, CD4+T cells, neutrophils and macrophages. CONCLUSION: HRGs have an important role in the prognosis of bladder cancer patients and may serve as new predictive biomarkers and potential targets for treatment.

[Research Progress of the Roles of Ubiquitination/Deubiquitination in Androgen Receptor Abnormalities and Prostate Cancer].

Ubiquitin is a small molecule protein consisting of 76 amino acids,widely found in eukaryotic cells. The process by which ubiquitin binding to a specific protein is called ubiquitination. Deubiquitination is the reversed process of ubiquitination. Ubiquitination stimulates downstream signal,including complex assembly,protein conformation and activity changes,proteolysis,autophagy,guilt,chromatin remodeling,and DNA repair. More than 80% of eukaryotic protein degradation is mediated by the ubiquitination system,and ubiquitin-dependent proteolysis is an extremely complex process involving many biomolecular processes. By regulating protein homeostasis,ubiquitination can also regulate a variety of biological processes including cell cycle,cell proliferation,and apoptosis,which are closely related to tumorigenesis and progression. Many abnormalities of androgen receptor (AR) including AR gene amplification,mutation,shear mutation,and AR activity enhancement are closely related to prostate cancer progression. In particular,prostate cancer progression is regulated by the ubiquitination/deubiquitination processes. This article summarizes the recent research advances in the roles of ubiquitination/deubiquitination in AR abnormalities and prostate cancer.

[Clinical Features and Diagnosis of Encrusted Bladder Cancer].

Bladder cancer is a urological malignant tumor with high morbidity and mortality. Masses protruding into the bladder cavity is an important feature for clinical diagnosis of bladder cancer. However,patients with encrusted bladder cancer(EBC)do not present with masses protruding into the bladder cavity and thus this malignancy is often misdiagnosed. Four patients were admitted in Peking University People's Hospital from July 2015 to February 2017. All of them were males aged 40 to 77 years(mean:58 years). Patients were mainly manifested as frequent urination,urgency,nocturia,and decreased bladder capacity,with or without difficulty of voiding.Although the bladder walls were markedly thickened,there was no obvious mass on imaging scans. Three patients received urodynamic test,which showed the maximum capacity of the bladder was 41 to 128 ml(mean:91 ml). One patient presented with gross hematuria,two patients presented with microscopic hematuria,and the remaining one patient had no hematuria. No mass was observed by cystoscopy. All of the patients were diagnosed with bladder cancer by repeated biopsy or intraoperative frozen section analysis.

Research Advances in Chemokine-like Factor Super Family Member 8.

Chemokine-like factor super family member (CMTM) is a novel generic family firstly reported by Peking University Center for Human Disease Genomics. CMTM8 is one member of this family and has exhibited tumor-inhibiting activities. It can encode proteins approaching to the transmembrane 4 superfamily. CMTM8 is down-regulated in most carcinoma cell lines and tissues. Over-expression of CMTM8 may inhibit the proliferation,migration,and invasion of carcinoma cells. However,the exact mechanism of its anti-tumor activity remains unclear. CMTM8 may be involved in various signaling pathways governing the occurrence and development of tumors. CMTM8 may be a new target in the gene therapies for tumors,while further studies on CMTM8 and its anti-tumor mechanisms are warranted.

[Research progress on unicompartmental knee arthroplasty for elderly patients with knee osteoarthritis].

Objective: To conclude the research progress of unicompartmental knee arthroplasty (UKA) in the treatment of elderly patients with knee osteoarthritis (KOA). Methods: The literature on UKA at home and abroad in recent years was reviewed to summarize the clinical characteristics of elderly patients with KOA, perioperative management (including evaluating indications preoperatively, intraoperative prosthesis selection, postoperative complication management, etc). Results: Through reasonable preoperative evaluation, prosthesis selection, and advanced perioperative management, for elderly patients with KOA who meet the indications, UKA can be considered. Compared with total knee arthroplasty, the incidence of postoperative complications in elderly patients undergoing UKA is lower, joint awareness is reduced, functional improvement and satisfaction are higher. Meanwhile, choosing appropriate prostheses and fixation methods can lead to a good survival rate. Conclusion: UKA can provide a safe and effective treatment option for elderly patients with KOA within a certain range of indications.

Combined association of dietary fibre and cognitive function with all-cause and cause-specific mortality in older adults.

BACKGROUND: Dietary fibre and cognitive function are associated with the risk of mortality, respectively. Inadequate dietary fibre intake and cognitive impairment frequently co-occur in older adults, but the combined effect of dietary fibre and cognitive function on mortality remains unknown. The study was to investigate the combined effect of dietary fibre and cognitive function on mortality over a 13-year follow-up in a representative of older adults from the U.S. METHODS: We analyzed data from two cycles of the National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2001-2002 with mortality follow-up data through 13 December 2015 obtained from Public-use Linked Mortality Files. Low dietary fibre intake was defined as the lowest quartile of dietary fibre intake. Cognitive impairment was defined as below the median of Digit Symbol Substitution Test. The separate and combined effects of low dietary fibre intake and cognitive impairment on all-cause and cause-specific mortality were assessed in older adults using weighted Cox proportional hazard models adjusting for potential confounders. RESULTS: A total of 2012 participants (weighted sample was 32,765,094) aged 60 years and older were enrolled in the study. After a median follow-up of 13.4 years, 1017 participants (50.4%) were identified as all-cause deaths, including 183 (9.1%) participants dying from cancer, 199 (9.9%) participants dying from cardiovascular disease, and 635 (31.5%) participants dying from non-cancer/non-cardiovascular disease. Participants with low dietary fibre intake and cognitive impairment had nearly twice the risk of all-cause (HR, 2.030; 95% CI, 1.406-2.931) and non-cancer/non-cardiovascular (HR, 2.057; 95% CI, 1.297-3.262) mortality, and over triple cancer (HR, 3.334; 95% CI, 1.685-6.599) mortality, compared to those without both. CONCLUSIONS: The combination of low dietary fibre intake and cognitive impairment was associated with an increased risk of all-cause, cancer and non-cancer/non- cardiovascular mortality in older adults.

Key MessagesThe inadequate dietary fibre intake and cognitive impairment often coexist in older adults, but the combined effect of dietary fibre and cognitive function on mortality is still unknown.This study evaluated the combined effect of dietary fibre and cognitive impairment on mortality among older adults with a 13-year follow-up in the United States, based on the National Health and Nutrition Examination Survey (NHANES).The results provided evidence of the importance of early screening and intervention for dietary fibre intake and cognitive function, and suggested the joint effect of dietary fibre and cognitive function on mortality could be significant for public health in older adults.

Ascending aorta dilatation reduces the influence of elevated pulse pressure on left ventricular hypertrophy: findings from a Chinese elderly hypertensive population.

OBJECTIVE: To determine the role of ascending aorta dilatation in the relationship between pulse pressure (PP) and left ventricular (LV) hypertrophy. METHODS: A total of 1556 Chinese elderly hypertensive patients were retrospectively studied. Transthoracic echocardiography was used to obtain the aortic and cardiac structure measurements. In addition, brachial blood pressure was measured, and total arterial compliance, systemic vascular resistance, arterial elastance, and end-systolic LV elastance were calculated. The participants were divided into four groups according to the status of ascending aortic diameter and PP. RESULTS: LV mass index increased in succession in the four groups, i.e., the group with the normal aorta and lower PP, with the normal aorta and higher PP, with aortic dilatation and lower PP, and with aortic dilatation and higher PP (P trend < 0.001). Total arterial compliance-1, arterial elastance, and end-systolic LV elastance were slightly higher in the individuals with normal aorta compared to those with aortic dilatation, regardless of PP being lower or higher (P < 0.01). Compared to the group with the normal aorta and lower PP, individuals with aortic dilatation had a significantly increased multivariable adjusted risk of LV hypertrophy, and higher PP further exacerbated this risk [aortic dilatation with lower PP (OR = 1.75, 95% CI: 1.01-3.04) and aortic dilatation with higher PP (OR = 3.42, 95% CI: 2.03-5.77)]. In the relation between PP and LV mass index (ß = 0.095, P < 0.001), -41.3% of the total effect was attributable to mediation by ascending aortic diameter (P < 0.0001). CONCLUSIONS: In Chinese elderly patients with hypertension, ascending aorta dilatation could reduce the influence of elevated PP on LV hypertrophy.

The multicomponent reaction of imidazo[1,5-a]pyridine carbenes with phthalaldehydes and dimethyl acetylenedicarboxylate: a facile construction of benzo[d]furo[3,2-b]azepines.

A study on the multicomponent reaction comprising both N-heterocyclic carbenes and substituted phthalaldehydes is reported. The imidazo[1,5-a]pyridine carbenes, namely imidazo[1,5-a]pyridine-3-ylidenes, reacted with phthalaldehydes and DMAD under very mild conditions to produce novel fused tricyclic benzo[d]furo[3,2-b]azepine derivatives. The resulting fused heterocyclic compounds are fluorescent and they give an emission around 500 nm with quantum yields (Φ(F)) being up to 0.81. This study provides not only a unique approach to fused azepine derivatives that are not easily accessible by other methods, but also opens a new avenue to complicated molecular skeletons. The fluorescence properties of long emission wavelength and high fluorescence quantum yields of some products predict their potential applications as optical sensors.

The School Attachment Monitor-A novel computational tool for assessment of attachment in middle childhood.

BACKGROUND: Attachment research has been limited by the lack of quick and easy measures. We report development and validation of the School Attachment Monitor (SAM), a novel measure for largescale assessment of attachment in children aged 5-9, in the general population. SAM offers automatic presentation, on computer, of story-stems based on the Manchester Child Attachment Story Task (MCAST), without the need for trained administrators. SAM is delivered by novel software which interacts with child participants, starting with warm-up activities to familiarise them with the task. Children's story completion is video recorded and augmented by 'smart dolls' that the child can hold and manipulate, with movement sensors for data collection. The design of SAM was informed by children of users' age range to establish their task understanding and incorporate their innovative ideas for improving SAM software. METHODS: 130 5-9 year old children were recruited from mainstream primary schools. In Phase 1, sixty-one children completed both SAM and MCAST. Inter-rater reliability and rating concordance was compared between SAM and MCAST. In Phase 2, a further 44 children completed SAM complete and, including those children completing SAM in Phase 1 (total n = 105), a machine learning algorithm was developed using a "majority vote" procedure where, for each child, 500 non-overlapping video frames contribute to the decision. RESULTS: Using manual rating, SAM-MCAST concordance was excellent (89% secure versus insecure; 97% organised versus disorganised; 86% four-way). Comparison of human ratings of SAM versus the machine learning algorithm showed over 80% concordance. CONCLUSIONS: We have developed a new tool for measuring attachment at the population level, which has good reliability compared to a validated attachment measure and has the potential for automatic rating-opening the door to measurement of attachment in large populations.

Multicomponent reaction of imidazo[1,5-a]pyridine carbenes with aldehydes and dimethyl acetylenedicarboxylate or allenoates: a straightforward approach to fully substituted furans.

The facile three-component reactions of N,N-substituted imidazo[1,5-a]pyridine carbenes, namely imidazo[1,5-a]pyridin-3-ylidenes, with aldehydes and DMAD or allenoates were disclosed. Both reactions proceeded via tandem nucleophilic addition, [3 + 2]-cycloaddition, and ring transformation to produce different 4-[(2-pyridyl)methyl]aminofuran derivatives generally in moderate yields. This work not only provided the first example of the application of imidazo[1,5-a]pyridin-3-ylidenes in organic synthesis but also developed a straightforward approach to fully substituted furans that are not easily accessible by other methods.

Map-based cloning and characterization of the novel yellow-green leaf gene ys83 in rice (Oryza sativa).

Leaf-color mutants have been extensively studied in rice, and many corresponding genes have been identified up to now. However, leaf-color mutation mechanisms are diverse and still need further research through identification of novel genes. In the present paper, we isolated a leaf-color mutant, ys83, in rice (Oryza sativa). The mutant displayed a yellow-green leaf phenotype at seedling stage, and then slowly turned into light-green leaf from late tillering stage. In its yellow leaves, photosynthetic pigment contents significantly decreased and the chloroplast development was retarded. The mutant phenotype was controlled by a recessive mutation in a nuclear gene on the short arm of rice chromosome 2. Map-based cloning and sequencing analysis suggested that the candidate gene was YS83 (LOC_Os02g05890) encoding a protein containing 165 amino acid residues. Gene YS83 was expressed in a wide range of tissues, and its encoded protein was targeted to the chloroplast. In the mutant, a T-to-A substitution occurred in coding sequence of gene YS83, which caused a premature translation of its encoded product. By introduction of the wild-type gene, the ys83 mutant recovered to normal green-leaf phenotype. Taken together, we successfully identified a novel yellow-green leaf gene YS83. In addition, number of productive panicles per plant and number of spikelets per panicle only reduced by 6.7% and 7.6%, respectively, meanwhile its seed setting rate and 1000-grain weight (seed size) were not significantly affected in the mutant, so leaf-color mutant gene ys83 could be used as a trait marker gene in commercial hybrid rice production.

[Effect of nano-SiO2 exposure on spatial learning and memory and LTP of hippocampal dentate gyrus in rats].

OBJECTIVE: To study the effect of nano-SiO2 on spatial learning and memory. METHODS: Twenty-four male rats were randomly divided into 3 groups: control group (C group), low dose group (L group) and high dose group (H group). The rats were intragastrically administrated with nanometer particles at 25 and 100 mg/kg body weight every day for 4 weeks. After exposure, the ability of learning and memory of rats was tested by Morris water maze, and electrophysiological brain stereotactic method was used to test long-tear potentiation (LTP) in dentate gyrus (DG) of the rats. RESULTS: The increase rate of body weight in H group was reduced significantly compared with C group ( P < 0.05). In the space exploration experiment of Morris water maze test, the escape latency of H group was longer than that of C group (P < 0.05). The rats of H group spent less time in finding the target quadrant (P < 0.05) . The rate of LP induction of H group was significantly lower than that of C group (P < 0.05). After high fre quency stimulation (HFS), The changes of amplitude of population spike (PS) of L group and H group were lower than those of C group significantly (P < 0.05, P < 0.01). CONCLUSION: Nano-SiO2may result in impairment of spatial learning and memory ability by reducing the rate of LTP induction and the increase of PS in hippocampus.